CYP11B1基因突变致11β-羟化酶缺陷症五例随访研究  

Five patients with 11β-hydroxylase deficiency due to CYP11B1 gene mutation: A case study

作　　者：杨海花[1] 李杨世玉 陈琼[1] 黄爱 苏畅[2] 陈永兴 卫海燕[1] Yang Haihua;Li Yangshiyu;Chen Qiong;Huang Ai;Su Chang;Chen Yongxing;Wei Haiyan(Children′s Hospital Affiliated to Zhengzhou University,Henan Children′s Hospital,Zhengzhou Children′s Hospital,Henan Provincial Key Laboratory of Children′s Genetics and Metabolic Diseases,Zhengzhou 450000,China;Department of Endocrinology,Genetics and Metabolism,Beijng Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijng 100045,China)

机构地区：[1]郑州大学附属儿童医院,河南省儿童医院郑州儿童医院,河南省儿童遗传代谢性疾病重点实验室,450000 [2]国家儿童医学中心首都医科大学附属北京儿童医院内分泌遗传代谢科,100045

出　　处：《中华内分泌代谢杂志》2023年第1期34-41,共8页Chinese Journal of Endocrinology and Metabolism

基　　金：河南省医学科技攻关计划联合共建项目 (LHGJ20210625)。

摘　　要：目的探索11β-羟化酶缺陷症(11β-hydroxylase deficiency,11β-OHD)患者的临床和遗传学特点,以提高对该病的认识。方法回顾性分析2016年至2021年在河南省儿童医院确诊的5例11β-OHD患儿的临床表现、激素水平、影像学检查、基因突变特点及随访结果。结果5例患儿中3例男性,2例女性,诊断时年龄1岁5个月~7岁(平均3岁9个月),骨龄3岁6个月~16岁(平均10岁3个月),均无阳性家族史,被误诊为21-羟化酶缺陷症(21-hydroxylase deficiency,21-OHD)2例,且长期合用盐皮质激素治疗。3例合并高血压,1例睾丸肾上腺残余瘤。5例肾上腺CT均提示肾上腺增粗,5例患儿ACTH、17-羟孕酮、睾酮、雄烯二酮不同程度地升高,低钾血症1例。基因分析结果为1例纯合突变,4例复合杂合突变,携带错义突变的4例,2例患者携带缺失,1例患者携带有CYP11B2 exon1-6/CYP11B1 exon7-9形成的嵌合基因。其中CYP11B1 c.1385T>C(p.L462P)、c.1354G>A(p.G452R)和c.64C>T(p.Q22*)为新的突变位点。随访结果:2例男性患儿终身高分别为164.4 cm和150.2 cm,余3例患儿复查相关激素水平正常。结论11β-OHD易于被误诊,导致终身高严重受损。CYP11B1基因突变复杂多样,需要多种基因检测手段协助分析。Objective To investigate the clinical and molecular characteristics of 11β-hydroxylase deficiency(11β-OHD)to improve the understanding of this disorder.Methods The clinical manifestation,hormone level,imaging examination,characteristics of gene variation and follow-up of five patients with 11β-OHD diagnosed in Henan Children′s Hospital from 2016 to 2021 were carefully reviewed.Results Among the 5 children,3 were male and 2 were female,all without positive family history.The age at diagnosis was 1 year 5 months to 7 years(average 3 years and 9 months),and the bone age was 3 years 6 months to 16 years(average 10 years and 3 months).Two cases were misdiagnosed as 21-hydroxylase deficiency(21-OHD)and treated with long-term mineralocorticoids.Three patients presented with hypertension and one patient had testicular adrenal rest tumor.Adrenal CT showed bilateral adrenal hyperplasia in five patients.ACTH,17-hydroxyprogesterone,testosterone,and androstenedione levels were increased in 5 children,and hypokalemia occurred in 1 patient.One patient carried homozygous novel missense variant,and four patients had compound heterozygous variants.Four patients carried missence mutations,two patients had deletion and one patient harbored a chimeric CYP11B2 exon1-6/CYP11B1 exon7-9.Three novel CYP11B1 mutations,including c.1385T>C(p.L462P),c.64C>T(p.Q22*)and c.1354G>A(p.G452R)were identified.The final height of 2 male children were 164.4 cm and 150.2 cm,respectively,and the related hormone levels of the other 3 children were normal.Conclusion 11β-OHD is easily misdiagnosed,leading to severe impairment of final height.CYP11B1 gene variation is complex and diverse,which requires variety of gene detection methods.

关 键 词：11β-羟化酶缺陷症 CYP11B1基因 CYP11B2/CYP11B1嵌合 

分 类 号：R725.9[医药卫生—儿科]